次黄苷三磷酸焦磷酸酶遗传多态性对硫嘌呤类药物疗效和不良反应影响的研究进展

硫嘌呤类药物作为一类常用的免疫抑制剂,广泛应用于临床.然而其治疗窗窄,药动学个体差异大一直是困扰该类药物临床应用的难题.尽管硫嘌呤甲基转移酶（thiopurine methyltransferase,TPMT）基因多态性被认为是影响硫嘌呤类药物药动学的主要遗传因素,但研究结论并不统一.而最近的一些研究将焦点集中到了次黄苷三磷酸焦磷酸酶（inosine triphosphate pyrophosphatase,ITPA）的遗传多态性上.因此,本文就ITPA遗传多态性对硫嘌呤类药物疗效和毒性影响的研究进展作一综述,以期为临床个体化应用硫嘌呤类药物提供理论指导.     

Protein expression of various hepatic uridine 5′‐diphosphate glucuronosyltransferase (UGT) enzymes and their inter‐correlations: a meta‐analysis

Avoiding cytochrome P450 (CYP) related drug interactions in the development of new drug candidates means that glucuronidation by uridine 5′‐diphosphate glucuronosyltransferase (UGT) enzymes is expected to become a more prominent pathway in the metabolism of new drug candidates designed by pharmaceutical companies. Therefore, determining the abundance and activity of these enzymes is of value in the process of scaling in vitro data to in vivo metabolic parameters. Many of the studies involving the measurement of UGTs were conducted with too few samples, which did not provide a good indication of population values and the level of variability. Meta‐analysis is used in the current study to combine all reported values (eight studies that used LC‐MS isotope‐labelled standard targeted quantitative methods), detect inconsistencies between the various datasets and describe correlations of expression between the quantified UGT enzymes. Some heterogeneity was observed between studies, especially in the UGT1A4, 2B7 and 2B10 datasets. However, in the absence of information on the inter‐laboratory consistency of assays, it is difficult to assign these differences to the heterogeneity of the samples. Large inter‐individual variability was observed in the collated data across this family of enzymes. Positive correlations between the expression levels of certain UGT enzymes were found in the collated data. These included the pairs: UGT1A4/2B4 (r_s = 0.71, p < 0.0001, n = 82), UGT2B4/2B15 (r_s = 0.63, p < 0.0001, n = 83), UGT2B7/2B15 (r_s = 0.81, p < 0.0001, n = 99). These correlations can be explained by common regulatory mechanisms involved in the expression of these proteins. Copyright © 2014 John Wiley & Sons, Ltd.     

2011-2013年包头市个体诊所消毒监测结果分析

目的对包头市个体诊所(包括村卫生室)的消毒卫生状况进行调查研究,为改进基层医疗单位消毒卫生质量和预防医源性感染提供参考。方法采取现场随机抽样检测的方法对包头市个体诊所空气卫生质量、物体表面、医护人员手、使用中的消毒液、紫外线灯辐照强度等进行消毒质量监测。结果 2011-2013年消毒灭菌监测总合格率呈逐年上升趁势:2011年77.63%,2012年79.10%,2013年80.94%。结论个人诊所存在消毒不严格、医护人员消毒意识不强等问题,为院内感染及医源性传染病的发生埋下了隐患。因此,应加大个人诊所消毒监测管理力度,增强医护人员规范消毒意识。     

超声在剖宫产瘢痕妊娠诊断及治疗中的应用价值

目的探讨经腹及经阴道联合超声对剖宫产瘢痕妊娠(caesarean scar pregnancy,CSP)诊断的临床价值,以及CSP的超声分型对临床个性化治疗CSP的指导价值。方法回顾分析河南科技大学第一附属医院超声诊断28例CSP住院患者声像图特征,及其保守治疗、手术治疗和病理结果及患者转归情况。结果 28例均获得明确诊断,将CSP分四型,孕囊型6例,结节型9例,团块型8例,巨块型5例;3例孕囊型为超声及临床确诊,25例均获得病理标本,其中24例显微镜下可见绒毛组织,1例病理确诊为绒癌,诊断正确率为96.4%。结论超声早期诊断CSP具有重要价值,而且对CSP的个性化治疗具有重要指导价值。     

Individual Differences in Attentional Bias Associated with Cocaine Dependence Are Related to Varying Engagement of Neural Processing Networks

Cocaine and other drug dependencies are associated with significant attentional bias for drug use stimuli that represents a candidate cognitive marker of drug dependence and treatment outcomes. We explored, using fMRI, the role of discrete neural processing networks in the representation of individual differences in the drug attentional bias effect associated with cocaine dependence (AB-coc) using a word counting Stroop task with personalized cocaine use stimuli (cocStroop). The cocStroop behavioral and neural responses were further compared with those associated with a negative emotional word Stroop task (eStroop) and a neutral word counting Stroop task (cStroop). Brain–behavior correlations were explored using both network-level correlation analysis following independent component analysis (ICA) and voxel-level, brain-wide univariate correlation analysis. Variation in the attentional bias effect for cocaine use stimuli among cocaine-dependent men and women was related to the recruitment of two separate neural processing networks related to stimulus attention and salience attribution (inferior frontal–parietal–ventral insula), and the processing of the negative affective properties of cocaine stimuli (frontal–temporal–cingulate). Recruitment of a sensory–motor–dorsal insula network was negatively correlated with AB-coc and suggested a regulatory role related to the sensorimotor processing of cocaine stimuli. The attentional bias effect for cocaine stimuli and for negative affective word stimuli were significantly correlated across individuals, and both were correlated with the activity of the frontal–temporal–cingulate network. Functional connectivity for a single prefrontal–striatal–occipital network correlated with variation in general cognitive control (cStroop) that was unrelated to behavioral or neural network correlates of cocStroop- or eStroop-related attentional bias. A brain-wide mass univariate analysis demonstrated the significant correlation of individual attentional bias effect for cocaine stimuli with distributed activations in the frontal, occipitotemporal, parietal, cingulate, and premotor cortex. These findings support the involvement of multiple processes and brain networks in mediating individual differences in risk for relapse associated with drug dependence.     

Dissociable Contributions of Anterior Cingulate Cortex and Basolateral Amygdala on a Rodent Cost/Benefit Decision-Making Task of Cognitive Effort

Personal success often requires the choice to expend greater effort for larger rewards, and deficits in such effortful decision making accompany a number of illnesses including depression, schizophrenia, and attention-deficit/hyperactivity disorder. Animal models have implicated brain regions such as the basolateral amygdala (BLA) and anterior cingulate cortex (ACC) in physical effort-based choice, but disentangling the unique contributions of these two regions has proven difficult, and effort demands in industrialized society are predominantly cognitive in nature. Here we utilize the rodent cognitive effort task (rCET), a modification of the five-choice serial reaction-time task, wherein animals can choose to expend greater visuospatial attention to obtain larger sucrose rewards. Temporary inactivation (via baclofen–muscimol) of BLA and ACC showed dissociable effects: BLA inactivation caused hard-working rats to ‘slack off'' and ‘slacker'' rats to work harder, whereas ACC inactivation caused all animals to reduce willingness to expend mental effort. Furthermore, BLA inactivation increased the time needed to make choices, whereas ACC inactivation increased motor impulsivity. These data illuminate unique contributions of BLA and ACC to effort-based decision making, and imply overlapping yet distinct circuitry for cognitive vs physical effort. Our understanding of effortful decision making may therefore require expanding our models beyond purely physical costs.